1ryv

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{{Seed}}
 
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[[Image:1ryv.png|left|200px]]
 
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==Three dimensional solution structure of the K27A MUTANT of sodium channels inhibitor HAINANTOXIN-IV BY 2D 1H-NMR==
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The line below this paragraph, containing "STRUCTURE_1ryv", creates the "Structure Box" on the page.
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<StructureSection load='1ryv' size='340' side='right'caption='[[1ryv]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1ryv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Haplopelma_hainanum Haplopelma hainanum]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RYV FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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{{STRUCTURE_1ryv| PDB=1ryv | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ryv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ryv OCA], [https://pdbe.org/1ryv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ryv RCSB], [https://www.ebi.ac.uk/pdbsum/1ryv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ryv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/H4A01_CYRHA H4A01_CYRHA] Neurotoxin that selectively inhibits neuronal tetrodotoxin-sensitive voltage-gated sodium channels (Nav) (IC(50)=44.6 nM) (PubMed:12518233, PubMed:14512091). It is active on Nav1.2/SCN2A (IC(50)=22.4 nM), Nav1.6/SCN8A (IC(50)=50.1 nM) and Nav1.7/SCN9A (IC(50)=48.9 nM) (PubMed:29703751). It shows low affinity for lipid bilayers (PubMed:29703751).<ref>PMID:12518233</ref> <ref>PMID:12827284</ref> <ref>PMID:14512091</ref> <ref>PMID:29703751</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Hainantoxin-IV (HNTX-IV) can specifically inhibit the neuronal tetrodotoxin-sensitive sodium channels and defines a new class of depressant spider toxin. The sequence of native HNTX-IV is ECLGFGKGCNPSNDQCCKSSNLVCSRKHRWCKYEI-NH(2). In the present study, to obtain further insight into the primary and tertiary structural requirements of neuronal sodium channel blockers, we determined the solution structure of HNTX-IV as a typical inhibitor cystine knot motif and synthesized four mutants designed based on the predicted sites followed by structural elucidation of two inactive mutants. Pharmacological studies indicated that the S12A and R26A mutants had activities near that of native HNTX-IV, while K27A and R29A demonstrated activities reduced by 2 orders of magnitude. (1)H MR analysis showed the similar molecular conformations for native HNTX-IV and four synthetic mutants. Furthermore, in the determined structures of K27A and R29A, the side chains of residues 27 and 29 were located in the identical spatial position to those of native HNTX-IV. These results suggested that residues Ser(12), Arg(26), Lys(27), and Arg(29) were not responsible for stabilizing the distinct conformation of HNTX-IV, but Lys(27) and Arg(29) were critical for the bioactivities. The potency reductions produced by Ala substitutions were primarily due to the direct interaction of the essential residues Lys(27) and Arg(29) with sodium channels rather than to a conformational change. After comparison of these structures and activities with correlated toxins, we hypothesized that residues Lys(27), Arg(29), His(28), Lys(32), Phe(5), and Trp(30) clustered on one face of HNTX-IV were responsible for ligand binding.
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===Three dimensional solution structure of the K27A MUTANT of sodium channels inhibitor HAINANTOXIN-IV BY 2D 1H-NMR===
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Structure--activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers.,Li D, Xiao Y, Xu X, Xiong X, Lu S, Liu Z, Zhu Q, Wang M, Gu X, Liang S J Biol Chem. 2004 Sep 3;279(36):37734-40. Epub 2004 Jun 16. PMID:15201273<ref>PMID:15201273</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The line below this paragraph, {{ABSTRACT_PUBMED_15201273}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1ryv" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 15201273 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15201273}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Haplopelma hainanum]]
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1RYV is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYV OCA].
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[[Category: Large Structures]]
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[[Category: Gu X]]
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==Reference==
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[[Category: Li D]]
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Structure--activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers., Li D, Xiao Y, Xu X, Xiong X, Lu S, Liu Z, Zhu Q, Wang M, Gu X, Liang S, J Biol Chem. 2004 Sep 3;279(36):37734-40. Epub 2004 Jun 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15201273 15201273]
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[[Category: Liang S]]
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[[Category: Single protein]]
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[[Category: Lu S]]
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[[Category: Gu, X.]]
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[[Category: Li, D.]]
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[[Category: Liang, S.]]
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[[Category: Lu, S.]]
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[[Category: Inhibitor cystine knot motif]]
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[[Category: Neurotoxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:14:37 2008''
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Current revision

Three dimensional solution structure of the K27A MUTANT of sodium channels inhibitor HAINANTOXIN-IV BY 2D 1H-NMR

PDB ID 1ryv

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